The establishment of viral persistence generally requires evasion of the host CD8+ T cell response. Here we describe a form of evasion wherein the CD8+ T cells are fully capable of recognizing their cognate antigen but their effector functions are suppressed by regulatory T cells. Virus-specific CD8+ T cells adoptively transferred into mice persistently infected with Friend virus proliferated and appeared activated, but failed to produce IFNγ or reduce virus loads. Cotransfer experiments revealed that a subpopulation of CD4+ T cells from persistently infected mice suppressed IFNγ production by the CD8+ T cells. Treatment of persistently infected mice with anti-GITR antibody to ameliorate suppression by regulatory T cells significantly improved IFNγ production by transferred CD8+ T cells and allowed a significant reduction in viral loads. The results indicate that CD4+ regulatory T cells contribute to viral persistence and demonstrate an immunotherapy for treating chronic retroviral infections.
Bibliographical noteFunding Information:
This work was supported by the NIAID intramural research program and by a grant to U.D. from the Deutsche Forschungsgemeinschaft (Di 714/6-1/2).